Evaluation of Hypoglycemia with Oral Hypoglycemic Agents by Using Spontaneous Adverse Event Reports Database

Abstract

Hypoglycemia with oral hypoglycemic agents (OHAs) is a major clinical problem in patients with type 2 diabetes mellitus. This study evaluated the relationship between OHAs treatment and hypoglycemia using spontaneous adverse event reports database such as the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) database. We found FAERS to contain 5,821,354 reports from January 2004 to June 2014 and JADER to contain 338,224 reports from April 2004 to November 2014. In FAERS and JADER, the lower limits of 95% confidence intervals of reporting odds ratio (ROR) for hypoglycemia reports were > 1 in most OHAs. The RORs indicate that hypoglycemia is likely associated with glimepiride and glibenclamide in sulfonylurea. The RORs in sulfonylurea and glinide increased with co-administration of alpha-glucosidase inhibitors. We applied the weibull shape parameter to time-to-event data in the JADER database. The shape parameter β of most OHAs were less than 1, which indicates that the hazard was considered to decrease over time. OHAs drug polypharmacy may influence signal strength, and may be associated with hyperglycemia. After considering the causality restraints of the current analysis, further robust epidemiological studies are recommended.